BACKGROUND: Mutations in the progranulin gene on chromosome 17(GRN) is considered as one of most common causes of frontotemporal lobe degeneration. However, the phenotype and genotype correlation of GRN varies among different cohorts and ethnicities. In Chinese people, the genotype of GRN has not been fully elucidated.
METHODS: 1945 patients with dementia at Peking Union Medical College Hospital underwent next-generation sequencing (NGS) analysis. GRN variations classified as likely pathogenic and of uncertain significance were identified. Demographic information, clinical presentations, and neuroimaging were collected. The clinical, neuropsychological and neuroimaging characters were investigated.
RESULTS: Three patients with four likely pathogenic mutation: p.P50fs & p.W49_P50delinsX, p.P439fs, p.R110X, and thirteen patients with uncertain significance mutations were enrolled. Cognitive dysfunction, behavior, and personality changes as well as aphasia were the most common presentations. Asymmetrical atrophy of the frontal lobe and temporal lobe appeared in 64% GRN mutation carriers. Parietal lobe dysfunction or parietal lobe atrophy existed in all patients. White matter lesions existed in 79% patients. The majority of clinical phenotype was frontotemporal lobe degeneration, though cerebral vascular lesions were obvious in some of them especially among old onset patients. The proportion of ApoE e4 carriers were higher in old onset patients than those in young onset ones.
CONCLUSIONS: GRN mutation is rare in Chinese dementia patients. The phenotype and genotype correlation is specific and overlaps.

OBJECTIVE: To investigate iron and myelin changes in deep gray matter (DGM) of relapsing-remitting multiple sclerosis (RRMS) patients and their relationship to atrophy by χ-separation imaging.
METHODS: 33 RRMS patients and 34 healthy controls (HC) were included in this study. The χ-separation map reconstructed from a 3D multi-echo gradient echo scan was used to measure the positive susceptibility (χpos) and negative susceptibility (χneg) of DGM. To take into account the effect of atrophy, susceptibility mass of DGM was calculated by multiplying volume by the mean bulk susceptibility. Differences in MRI metrics between baseline patients, follow-up patients, and HC were compared respectively.
RESULTS: Compared to HC, χpos of basal ganglia were significantly increased in follow-up patients (P < 0.05). The χpos of pallidum was significantly higher in follow-up patients than that in baseline patients (P = 0.006). The χneg of caudate, pallidum and hippocampus in baseline and follow-up patients was significantly higher than that in HC (P < 0.05). When taking into account the effect of atrophy, there was a significant decrease in χpos mass and a significant increase in χneg mass of thalamus, accumbens and amygdala in follow-up patients compared to HC (P < 0.05). The χpos mass of the thalamus was further decreased in follow-up patients compared to baseline patients (P = 0.006).
CONCLUSIONS: χ-separation imaging could generate independent information on iron and myelin changes in RRMS patients, showing atrophy-dependent iron increase in basal ganglia and atrophy-independent iron and myelin decrease in thalamus.

BACKGROUND: Ischemic stroke is one of the leading causes of chronic disability worldwide, and stroke-induced heart damage can lead to death. According to research, patients with a variety of brain disease have good clinical results after vagus nerve stimulation (VNS). After ischemic stroke, mast cells (MCs) degranulate and release a large number of mediators, which may cause systemic inflammation. Chymase secreted by MCs can increase the levels of pathological angiotensin II (AngⅡ), which plays a crucial role in the deterioration of heart disease. Our goal was to develop a minimally invasive, targeted, and convenient VNS approach to assess the impact of VNS and to clarify the relationship between VNS and MCs in the prognosis of patients with myocardial atrophy after acute ischemic stroke.
METHODS: In this study, we verified the role of VNS in the treatment of myocardial atrophy after stroke and its molecular mechanism using a rat model of middle cerebral artery occlusion (MCAO/r). Behavioral studies were assessed using neurobehavioral deficit scores. Enzyme-linked immunosorbent assays, immunofluorescence staining, Western blotting and qRT-PCR were used to analyze the expression levels of myocardial atrophy, MC and inflammatory markers in rat hearts.
RESULTS: VNS improved myocardial atrophy in MCAO/r rats, inhibited MC activation, reduced the expression of chymase and AngⅡ, and inhibited the expression of proinflammatory factors. The chymase activator C48/80 reversed these effects of VNS. Chymase activation inhibited the effect of VNS on myocardial atrophy in MCAO/r rats, increased AngⅡ expression and aggravated inflammation and autophagy. The myocardial atrophy of MCAO/r rats was improved after chymase inhibition, and AngⅡ expression, inflammation and autophagy were reduced. Our results suggest that VNS may reduce the expression of chymase and AngⅡ by inhibiting MC activation, thereby improving myocardial atrophy and reducing inflammation and autophagy in MCAO/r rats. Inhibition of MC activation may be an effective strategy for treating myocardial atrophy after stroke.
CONCLUSIONS: VNS inhibits MC activation and reduces the expression of chymase and AngII, thereby alleviating myocardial atrophy, inflammation and autophagy after stroke.

Cerebral small vessel disease (CSVD) is an important cause of stroke, cognitive impairment, and other diseases, and its early quantitative evaluation can significantly improve patient prognosis. Magnetic resonance imaging (MRI) is an important method to evaluate the occurrence, development, and severity of CSVD. However, the diagnostic process lacks quantitative evaluation criteria and is limited by experience, which may easily lead to missed diagnoses and misdiagnoses. With the development of artificial intelligence technology based on deep learning, the extraction of high-dimensional features in imaging can assist doctors in clinical decision-making, and it has been widely used in brain function and mental disorders, and cardiovascular and cerebrovascular diseases. This paper summarizes the global research results in recent years and briefly describes the application of deep learning in evaluating CSVD signs in MRI imaging, including recent small subcortical infarcts, lacunes of presumed vascular origin, vascular white matter hyperintensity, enlarged perivascular spaces, cerebral microbleeds, brain atrophy, cortical superficial siderosis, and cortical cerebral microinfarct.

BACKGROUND: Fractional picosecond lasers (FPL) are reported to be effective and safe for atrophic acne scars and post-acne erythema. However, there is no evidence regarding the effectiveness and safety of FPL treatment for non-acne atrophic scars and scar erythema among Chinese patients.
METHODS: In this retrospective study, 12 Chinese patients with non-acne atrophic scars, including nine with scar erythema, were treated with one to three sessions of 1064 nm FPL treatment. Clinical improvement was objectively assessed through blinded evaluations by external physicians. A modified Manchester Scar Scale (mMSS) and the Clinician Erythema Assessment Scale (CEAS) were individually used to evaluate atrophic scars and scar erythema based on photographs. Physician-assessed and subject-assessed Global Aesthetic Improvement Scale (GAIS) were used to assess changes before and after FPL treatment. Patient satisfaction and adverse events were also documented.
RESULTS: Total mMSS scores, as well as three parameters (color, distortion, and texture), were significantly decreased after FPL treatment, with a mean reduction of 3.18 ± 1.60 in total scores (p < 0.05). The CEAS scores were significantly reduced from 2.41 ± 0.98 before treatment to 0.41 ± 0.40 at the final visit (p < 0.05). Based on physician-assessed and subject-assessed GAIS scores, 11 (91.7%) patients were improved after FPL treatment. 33.3% of patients were very satisfied, and 41.7% were satisfied. No serious, prolonged (> 3 weeks) adverse events were observed.
CONCLUSIONS: Our study suggests that 1064 nm FPL treatment may be a promising option for non-acne atrophic scars, especially with scar erythema. Further studies are needed to confirm our results.

Research on the local hippocampal atrophy for early detection of dementia has gained considerable attention. However, accurately quantifying subtle atrophy remains challenging in existing morphological methods due to the lack of consistent biological correspondence with the complex curving regions like the hippocampal head. Thereby, this article presents an innovative axis-referenced morphometric model (ARMM) that follows the anatomical lamellar organization of the hippocampus, which capture its precise and consistent longitudinal curving trajectory. Specifically, we establish an \"axis-referenced coordinate system\" based on a 7 T ex vivo hippocampal atlas following its entire curving longitudinal axis and orthogonal distributed lamellae. We then align individual hippocampi by deforming this template coordinate system to target spaces using boundary-guided diffeomorphic transformation, while ensuring that the lamellar vectors adhere to the constraint of medial-axis geometry. Finally, we measure local thickness and curvatures based on the coordinate system and boundary surface reconstructed from vector tips. The morphometric accuracy is evaluated by comparing reconstructed surfaces with those directly extracted from 7 T and 3 T MRI hippocampi. The results demonstrate that ARMM achieves the best performance, particularly in the curving head, surpassing the state-of-the-art morphological models. Additionally, morphological measurements from ARMM exhibit higher discriminatory power in distinguishing early Alzheimer\'s disease from mild cognitive impairment compared to volume-based measurements. Overall, the ARMM offers a precise morphometric assessment of hippocampal morphology on MR images, and sheds light on discovering potential image markers for neurodegeneration associated with hippocampal impairment.

Objective: To quantify cerebral cortical and deep gray matter atrophy in patients with multiple sclerosis (MS) and explore its correlation with impairment in domains of cognitive function. Methods: Twenty patients with MS and 16 healthy controls (HC) matched for age, sex, and education level were included. Using FreeSurfer software, based on 3D-MRI technology, the differences in cortical thickness and deep gray matter volume between the two groups were comparatively analyzed. A neuropsychological scale that included six domains of cognitive function was scored on both study groups to analyze the correlation between cortical thickness and volume of deep gray matter in MS patients with impairment in cognitive function domains. Results: Impairment in domains of cognitive function: cognitive impairment was present in 60% MS patients in this study, mainly manifesting as impairment of verbal memory, verbal fluency, visuospatial memory, and information processing speed function (all P<0.05). Of these, the majority had impaired visuospatial memory function (55.0%), and the least number of patients had impaired information processing speed (15.0%). Changes in cortical thickness: compared with the HC group, the MS group showed that cortical atrophy was mainly concentrated in the frontoparietal region, including significant thinning of cortical thickness in the left inferior parietal gyrus, right superior frontal gyrus, and the right superior parietal gyrus (all P<0.05). Among them, atrophy of the left inferior parietal gyrus was significantly positively correlated with the impairment of verbal memory, verbal fluency, and information processing speed (all P<0.05). There was a significant positive correlation between the right superior frontal gyrus atrophy and verbal memory, verbal fluency, and visuospatial memory impairment (all P<0.05). Changes in deep gray matter volume: compared with the HC group, deep gray matter volume in the MS group decreased significantly in the bilateral thalamus, bilateral putamen, bilateral pallidum (all P<0.01), and right nucleus accumbens (P<0.05). Among them, left thalamus atrophy was significantly positively correlated with visuospatial memory impairment (r=0.45, P=0.046), and left putamen atrophy was both significantly positively correlated with visuospatial memory (r=0.45, P=0.047) and information processing speed impairment (r=0.50, P=0.026). Conclusions: Early structural brain changes in MS are dominated by gray matter atrophy. Deep gray matter is more prominent than cortical atrophy.
目的： 量化分析多发性硬化（MS）患者脑皮质及深部灰质萎缩情况，探索其与认知功能领域损害的相关性。 方法： 横断面研究。纳入2022年10月至2023年10月就诊于解放军总医院第六医学中心的MS患者20例及年龄、性别、教育水平相匹配的健康对照组16名，使用FreeSurfer软件，基于3D-MRI技术，对比分析两组皮质厚度及深部灰质体积差异，并对两组受试者进行包括6个认知功能领域在内的神经心理学量表评估，分析MS患者皮质厚度及深部灰质体积与认知功能领域损害的相关性。 结果： （1）认知功能领域受损情况：本研究60%的MS患者存在认知障碍，主要表现为言语记忆、言语流畅性、视空间记忆、信息处理速度功能受损（均P<0.05）。其中，以视空间记忆功能损害者居多（占55.0%），信息处理速度损害者最少（占15.0%）。（2）皮质厚度改变情况：与健康对照组相比，MS组皮质萎缩主要集中于额顶部，包括左侧顶叶下回、右侧额上回、右侧顶叶上回皮质厚度均显著变薄（均P<0.05）。其中，左侧顶叶下回萎缩与言语记忆、言语流畅性、信息处理速度损害间均呈显著正相关（均P<0.05），右侧额上回萎缩与言语记忆、言语流畅性、视空间记忆损害间均存在显著正相关（均P<0.05）。（3）深部灰质体积改变情况：与健康对照组相比，MS组深部灰质体积显著减少的区域有双侧丘脑、双侧壳核、双侧苍白球（均P<0.01）、右侧伏隔核（P<0.05）。其中，左侧丘脑萎缩与视空间记忆损害呈显著正相关（r=0.45，P=0.046），左侧壳核萎缩与视空间记忆（r=0.45，P=0.047）及信息处理速度损害（r=0.50，P=0.026）均存在显著正相关。 结论： MS患者脑结构改变早期以灰质萎缩为主。其中，深部灰质较皮质萎缩更为突出。MS患者认知障碍方面，以言语记忆、言语流畅性、信息处理速度及视空间记忆功能损害为主，且与相应功能区域脑萎缩显著相关。.

BACKGROUND: 3D-Slicer is an open-source medical image processing and visualization software. In the surgical treatment of trigeminal neuralgia, it is commonly used to predict the responsible vessels. However, there are few reports on the use of 3D-Slicer software to quantitatively measure the bilateral trigeminal nerve volume in patients with primary trigeminal neuralgia (PTN) based on the three-dimensional images. Therefore, this study aims to explore the role of three-dimensional fused images processed by 3D-Slicer in the evaluation of trigeminal nerve atrophy, providing an objective basis for the diagnosis of PTN.
METHODS: 57 PTN patients who underwent microvascular decompression (MVD) or percutaneous balloon compression (PBC) surgery in Hebei general hospital between January 2020 and April 2023 were included. Additionally, 30 patients with facial spasms(HFS) were included as a control group. All patients underwent 3D-TOF-MRA and 3D-FIESTA sequence examinations. Comparisons of bilateral trigeminal nerve volumes within and between groups were conducted by performing image fusion using 3D-slicer.
RESULTS: The volume of the affected trigeminal nerve in the MVD group (33.96 mm³±12.61 mm³) and PBC group (23.05 mm³±7.71 mm³) was smaller than that of the unaffected trigeminal nerve in the MVD group (39.61 mm³±12.83 mm³) and PBC group (26.14 mm³±6.42 mm³), as well as the average volume of the trigeminal nerve in the control group (40.27 mm³±10.25 mm³) (P<0.05). The differences in bilateral trigeminal ganglion volume (∆V) was significant between the MVD group (∆V=23.59 %±14.32 %) and the control group (∆V=14.64 %±10.00 %) (P<0.05). There was no statistical difference in the trigeminal nerve volume difference between the MVD group (∆V=23.59 %±14.32 %) and the PBC group (∆V=26.52 %±15.00 %) (P>0.05).
CONCLUSIONS: Trigeminal nerve atrophy is correlated with primary trigeminal neuralgia. 3D-slicer software can quantitatively measure trigeminal nerve volume and assist in the diagnosis of primary trigeminal neuralgia based on the difference in bilateral trigeminal nerve volumes. However, trigeminal nerve atrophy is not associated with postoperative pain recurrence in patients.

BACKGROUND: Recent studies have associated immune abnormalities with dementia. IL-6 is a crucial cytokine in inflammatory responses, and recent evidence has linked elevated IL-6 levels to changes in brain structure and cognitive decline. However, the connection between IL-6 levels, cognition, brain volumes, and dementia risk requires exploration in large prospective cohorts.
METHODS: This study utilized a longitudinal cohort from the UK Biobank to analyze the correlation between IL-6 expression levels, cognitive performance, and cortical and subcortical brain volumes through linear regression. Additionally, we assessed the association between IL-6 levels and long-term dementia risk using Cox regression analysis. We also used one-sample Mendelian randomization to analyze the impact of genetic predisposition of dementia on elevated IL-6 levels.
RESULTS: A total of 50,864 participants were included in this study, with 1,391 new cases of all-cause dementia identified. Higher plasma IL-6 levels are associated with cortical and subcortical atrophy in regions such as the fusiform, thalamus proper, hippocampus, and larger ventricle volumes. IL-6 levels are negatively associated with cognitive performance in pair matching, numeric memory, prospective memory, and reaction time tests. Furthermore, elevated IL-6 levels are linked to a 23-35 % increased risk of all-cause dementia over an average follow-up period of 13.2 years. The one-sample Mendelian randomization analysis did not show associations between the genetic predisposition of dementia and elevated IL-6 levels.
CONCLUSIONS: Increased IL-6 levels are associated with worse cognition, brain atrophy, and a heightened risk of all-cause dementia. Our study highlights the need to focus on the role of peripheral IL-6 levels in managing brain health and dementia risk.

Long-term blood pressure variability (BPV) and plasma neurofilament light (pNfL) have been identified as potential biomarkers for Alzheimer\'s disease (AD) and cerebral small vessel disease (CSVD). However, the relationship between BPV, pNfL, and their association with the comorbidity of AD and CSVD remains unknown.
Participants with normal cognition and mild cognitive impairment from the Alzheimer\'s Disease Neuroimaging Initiative study were included in the data analysis. Linear mixed-effects regression models and causal mediation analyses were conducted to investigate the relationship among BPV, pNfL, comorbidity-related brain structural changes (hippocampal atrophy and white matter hyperintensities [WMH]), and cognitive function.
BPV was associated with pNfL, volumes of hippocampus and WMH, and cognition. pNfL mediated the effects of BPV on brain structural changes and cognition.
Our findings suggest a potential role of BPV and pNfL in the mechanism of comorbidity between AD and CSVD, underscoring the importance of BPV intervention in the general population.
Individuals with both Alzheimer\'s disease (AD) and cerebral small vessel disease (CSVD) pathologies had elevated blood pressure variability (BPV) and plasma neurofilament light (pNfL). The association between different components of BPV and brain structural changes may vary. BPV was associated with pNfL levels independent of average blood pressure. pNfL mediated the effects of BPV on comorbidity-related brain structural changes and cognitive performance.